Sebastian, a Roman soldier turned Christian, was stripped and shot with arrows for shielding Christian martyrs in defiance of the Emperor. He is shown here under the care of Saint Irene, who miraculously removed the arrows and healed his wounds. Sebastian's triumph over his affliction led him to become the saint who was invoked against dangers like the plague. He is often portrayed in paintings from Naples, such as this one, that were painted after the city's terrible plague of 1656.

The shadowy forms in the central background are vestiges of an earlier Giordano work over which the artist painted this composition.